Lysosomes are being prepared from mouse liver and cultured HeLa cells by gradient centrifugation techniques. Lysosomes purified in this manner will be ruptured to prepare soluble and particulate fractions. Each fraction will be used separately to immunize rabbits. The resulting antisera will be used in a modified immunoelectrophoretic system to screen for abnormalities in selected inherited diseases, such as I-cell disease and Chediak-Higashi disease. Electrophoretic systems capable of separating human lysosomal enzymes from their rodent homologues will be developed for use in the examination of human rodent hybrids. The results of these studies will be used to analyze the genetic determinants of various human lysosomal enzymes.